Physical Activity, Cardiovascular Status, Mortality, and Prediabetes in Hispanic and Non-Hispanic Adults

Key Points Question Is meeting Physical Activity Guidelines for Americans (PAG) associated with cardiovascular disease (CVD) or mortality risk similarly for individuals with prediabetes and normoglycemia, and do the associations of activity with health outcomes differ between Hispanic or Latino and non-Hispanic persons? Findings In this cohort study of 13 223 adults with prediabetes or normoglycemia, not meeting PAG was associated with CVD or mortality risk in adults with normoglycemia but not in individuals with prediabetes in Hispanic or Latino and non-Hispanic cohorts. Meaning Because meeting PAG was not associated with lower CVD or mortality risk in adults with prediabetes, individuals may need to improve multiple lifestyle factors, including reducing sedentary behavior.


Introduction
Results from the US Diabetes Prevention Program show that lifestyle interventions can reduce type 2 diabetes incidence in individuals with risk factors. 1 While the association between mortality and physical activity (PA) has been studied in multiple cohorts, 2,3 data are limited for persons with prediabetes and Hispanic or Latino groups.Prediabetes is associated with higher risk of mortality and CVD 4 and is present in 34% of Americans, with estimated age-adjusted prevalence of 35.3% overall in Hispanic or Latino persons. 5Characteristics of Hispanic or Latino persons, such as high workplace exertion, may differ from the overall US population, justifying the need for Hispanic-or Latinospecific studies. 6More US data are needed on the effects of lifestyle interventions on health outcomes in prediabetes over longer follow-up, particularly in populations with a high burden of diabetes, which includes US Hispanic or Latino groups. 7r primary goal was to determine the association between PA and the composite outcome of all-cause mortality and incident cardiovascular disease (CVD) by prediabetes status and background: Hispanic or Latino and non-Hispanic.We studied this association in adults from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and from the primarily non-Hispanic White adults in the Framingham Heart Study (FHS) using accelerometer-measured moderate to vigorous PA (MVPA), the PA measure most readily harmonized between the 2 cohorts.To further study the association between movement and the composite outcome in Hispanic or Latino persons, we studied accelerometer-measured sedentary behavior, mean number of steps per day, mean accelerometer counts per minute, and calibrated activity-related energy expenditure (CAEE), which accounts for PA measurement error, 8 in HCHS/SOL.

HCHS/SOL and FHS Study Cohorts
The 2 cohort studies were approved by institutional review boards at each field center where all participants gave written informed consent.The present study conformed to the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) reporting guideline, 9 and where applicable, the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 10 guideline.
The HCHS/SOL and FHS collected in-person baseline examination data and incident events data during follow-up. 11,12The HCHS/SOL is a community-based prospective cohort study of 16 415 selfidentified Hispanic or Latino persons aged 18 to 74 years at screening from randomly selected households in four US field centers (Chicago, Illinois; Miami, Florida; Bronx, New York; and San Diego, California) during 2008 to 2011. 13The HCHS/SOL used a stratified 2-stage probability sample, with the first sampling stage involving randomly selected census block groups, and the second sampling stage involving random selection of household units within the selected geographic areas. 14

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Physical Activity, CVD, and Mortality by Glycemic Status in Hispanic and Non-Hispanic Adults The FHS participants 11 included the Generation 2 (Gen 2) cohort enrolled in 1971 (the offspring [and their spouses] of the original cohort who were sampled in the 1940s in Framingham, Massachusetts), 15 Gen 3 and new offspring spouses (NOS) cohorts enrolled in 2002 (children of the Gen 2 and spouses of Gen 2 not already enrolled in FHS), 12 and the Omni 1 and Omni 2 cohorts, who were recruited in 1994 and 2003, respectively, to reflect the greater ethnic diversity of Framingham. 16Our initial sample included 4381 participants from Gen 3, NOS, Omni 2, Gen 2, and Omni 1 who completed the index examination and had accelerometer data.

Assessment of PA/Sedentary Behavior
The FHS 17 and HCHS/SOL 18,19 used similar hip-worn accelerometers (Actical model 198-0200-03 in HCHS/SOL; Actical model 198-0200-00 in FHS; Respironics) to measure at least 7 days' PA at baseline.In HCHS/SOL, accelerometer counts classified sedentary behavior as fewer than 100 counts/min and MVPA as at least 1535 counts/min 18,19 with 1 minute epoch length.A subset of HCHS/SOL participants had activity-related energy expenditure measured using indirect calorimetry and doubly labeled water, enabling the derivation of CAEE for HCHS/SOL participants. 8The FHS accelerometer data were recorded in 30-second epochs, with MVPA classified as at least 1535 counts/min. 17Accelerometer data were preprocessed by removing the time the device was not worn using the Choi et al algorithm. 20r examination 4, Gen 2 or Omni 1) for FHS.We excluded participants having fewer than 3 accelerometer days with wear times at least 10 hours per day.

Inclusion Criteria
For HCHS/SOL, we used self-reported diagnosis of diabetes plus American Diabetes Association laboratory criteria to classify diabetes and prediabetes at baseline.Laboratory-based criteria were fasting more than 8 hours with glucose levels at least 126 mg/dL (100-125 mg/dL for prediabetes) (to convert serum glucose levels to millimoles per liter, multiply by 0.0555), or fasting 8 hours or less with glucose levels 200 mg/dL or higher, or glucose levels for an oral glucose tolerance test at least 200 mg/dL (140-199 mg/dL for prediabetes), or hemoglobin A 1C levels at least 6.5% of total

Outcomes
The composite outcome was defined as time to incident CVD event or death, whichever came first.
Event numbers were insufficient to support separate analyses for each outcome type.Follow-up time was from the baseline examination to proxy-reported death or first adjudicated CVD event through 2017 for HCHS/SOL and from the index examination through 2019 for FHS.In both cohorts, potential events were identified through annual follow-up surveys.When a hospitalization or death was reported, mechanisms to obtain the records were initiated, and physician reviewers classified the events.
In HCHS/SOL, incident CVD was defined as the first adjudicated definite or probable MI, primary All models in HCHS/SOL accounted for missing accelerometry data using inverse probability weighting and accounted for the complex survey design.We also performed a random-effects meta-analysis of the results from HCHS/SOL and FHS with subgroup analysis by glycemic classification.

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Physical Activity, CVD, and Mortality by Glycemic Status in Hispanic and Non-Hispanic Adults

Association of Accelerometry Metrics With Outcomes Among HCHS/SOL Participants
To further assess the association of PA and sedentary behavior by glycemic status with the composite outcome in Hispanic or Latino individuals, we fit Cox proportional hazards models with a prediabetes by PA or sedentary behavior interaction term to the HCHS/SOL data using counts per min, sedentary behavior, or steps as the primary exposure, with each modeled as continuous, binary, or in tertiles.
Where results appeared consistent across prediabetes and normoglycemia groups, these groups were combined.For binary exposures, steps were classified as fewer than 7000 steps/day vs 7000 steps/day or more, based on findings that 7000 steps/day is approximately consistent with a 150-minute/week MVPA. 22The counts per minute were dichotomized about the median value of 148.We dichotomized sedentary behavior as the lowest tertile (Յ607 minutes/day) vs the highest 2 tertiles (>607 minutes/day).We explored possible nonlinear associations between the continuous exposures and the composite outcome using restricted cubic splines with 4 knots set at quartiles of each PA and sedentary behavior exposure.Models included prediabetes by PA or prediabetes by SB interaction terms and were adjusted for age, sex, field center, Hispanic or Latino background, systolic blood pressure, LDL-C, BMI, smoking status, alcohol use, educational level, employment status, income, sleep duration, diet quality, 23 language preference, wear time, physician visit in the last year prior to baseline visit, and use of health insurance.All models were adjusted for complex survey design.As BMI, LDL-C levels, and systolic blood pressure could be considered mediators of the PA outcome association, we fit models in HCHS/SOL for binary and continuous MVPA, steps, counts per minute, and sedentary behavior exposures, with or without these terms, to confirm estimates.We modeled CAEE as a continuous exposure in calibration and outcome models separately for each glycemic group (eMethods in Supplement 1).

Sensitivity Analyses and Model Assumptions
Sensitivity analyses for MVPA in FHS and HCHS/SOL excluded participants with BMI lower than 18.5 or events in the first 1 to 2 years of follow-up to check for reverse causation. 24We fit separate models for individuals with prediabetes and normoglycemia to compare with interaction models.
Proportional hazards assumptions were verified with scaled Schoenfeld residual plots, addressing covariates with violations by stratification.
Statistical analyses were conducted between September 1, 2022, and January 10, 2024, using Stata 17 (StataCorp LLC) 25 for the meta-analysis and R, version 4.1.3(R Project for Statistical Computing), 26 or SAS, version 9.4 (SAS Institute Inc), 27 for all other analyses.A 2-sided value of P < .05 was considered statistically significant.

Baseline Characteristics
This cohort study included a total of 13 223 participants; after exclusions (Figure 1 in Supplement 1).
The test statistic for difference in HR between prediabetes and normoglycemia was 2.86 (χ 2 e Household income is reported for Gen 3/NOS/Omni 2.
f In FHS, education level reported for Gen 3, NOS, Omni 1 and Omni 2; years of education only reported for Gen 2.
h SF-12 component "limited in work or other activities due to physical health" response of "most or all of the time." i Hypertension defined as systolic blood pressure 140 mm Hg or higher, diastolic blood pressure 90 mm Hg or higher, or taking antihypertensive medication in the last 4 weeks.
j Hypercholesterolemia defined as total cholesterol 240 mg/dL or higher or LDL 160 mg/dL or higher or HDL less than 40 mg/dL or use of lipid lowering drugs.

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Physical Activity, CVD, and Mortality by Glycemic Status in Hispanic and Non-Hispanic Adults distribution, 1 df; P = .09).Heterogeneity between cohorts within the prediabetes and normoglycemia subgroups was not statistically significant.

Association of Outcomes With Other Accelerometer Measures in HCHS/SOL
Baseline characteristics of HCHS/SOL participants with lower vs higher counts per minute or steps largely mirrored the differences reported for not meeting vs meeting PAG (eTables 6 and 7 in Supplement 1).However, high sedentary behavior had additional correlates in HCHS/SOL beyond those associated with low PA: highest education level, English as preferred language, had health insurance, and had a physician visit within the last year (eTable 5 in Supplement 1).No statistically significant associations were found between the composite outcome and the additional measures in HCHS/SOL, although estimated HRs for the putative "unhealthy" vs "healthy" activity levels were consistently farther from the null in the normoglycemia group, favoring the "healthier" behavior (eg, HR, 1.23 [95% CI 0.69-2.21] in the normoglycemia group and 1.03 [95% CI 0.63-1.69] in the prediabetes group, for counts per minute below vs above the median) (Table 2).
In the HCHS/SOL normoglycemia group, for 3-category exposure models, we noted a monotonically increasing HR associated with CVD or mortality across declining MVPA and countsper-minute tertiles (Figure 3).We observed increasing HRs across successively higher SB tertiles in both HCHS/SOL groups (eg, HR, For continuous PA or sedentary behavior exposures in HCHS/SOL, HRs were near 1.00 (eTable 8A in Supplement 1).There was no statistically significant nonlinearity in the adjusted restricted cubic spline models.For each 50 kcal/day CAEE, the HRs were 0.98 (95% CI 0.85-1.15) in the prediabetes group and 0.98 (0.86-1.12) in the normoglycemia group (eTable 8A in Supplement 1).
Because HRs for sedentary behavior, steps, and CAEE were of similar magnitude and direction for both glycemic groups, we fit additional fully adjusted models combining glycemic groups.For sedentary behavior, the HR for the composite outcome in the combined group was 1.06 (95% CI, 0.99-1.13)per 30 minutes of sedentary behavior; P = .10(eTable 8B in Supplement 1).The meta-analysis combined glycemic groups across both studies using the randomeffects DerSimonian and Laird model.The overall test of group differences shown is for prediabetes vs normoglycemia (see Methods for details).The estimates of between-study variance (τ 2 ) are imprecise with only 2 studies.PAG indicates Physical Activity Guidelines for Americans.

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Physical Activity, CVD, and Mortality by Glycemic Status in Hispanic and Non-Hispanic Adults

Results From Sensitivity Analyses
With individuals with low BMI excluded, the results were similar to those in Figure 2.With participants excluded who had events within the first 1 or 2 years, PA-related HRs were similar but of smaller magnitude in both HCHS/SOL glycemic groups (eTable 9 in Supplement 1).For FHS, HRs were smaller in the prediabetes group when excluding individuals with events in the first 1 or 2 years (eTable 10 in Supplement 1).Separate models for the 2 glycemic groups gave results similar to those from the interaction models.

Discussion
In this cohort study of Hispanic or Latino adults from HCHS/SOL and largely non-Hispanic White adults from FHS, participants with normoglycemia who did not achieve at least 150 minutes/week of MVPA had a greater risk of mortality and CVD than those who met this target.Yet this association was not observed in adults with prediabetes.This pattern of results was observed in each cohort separately and in a meta-analysis of both cohorts.In HCHS/SOL, the association of the composite outcome with other PA measures was largely nonsignificant.The HRs for lower counts per minute and for steps were higher in the normoglycemia group than in the prediabetes group (Table 2), whereas the HR for greater sedentary behavior was in the same direction for the 2 glycemic groups (Figure 3 and eTable 8 in Supplement 1).
Results from several randomized clinical trials suggested that lifestyle modifications, including PA, may not reduce mortality and CVD risk in people with prediabetes. 4,28,29The Finnish Diabetes Prevention Study, 30 Da Qing Diabetes Prevention Study, 31,32 US Diabetes Prevention Program 1,33,34 and the Indian Diabetes Prevention Programme 35 all found that interventions of diet or exercise compared with control (routine or limited advice) reduced risk of progression from prediabetes to diabetes and in some cases improved CVD risk factors.However, none of these interventions had a clear effect on mortality or CVD events over follow-up times from 2.5 to 21 years.
b MVPA model shown here had more covariates and more granular categories than the model used for comparison with the Framingham Heart Study shown in Figure 2. Models included a prediabetes by PA or sedentary behavior interaction term and were adjusted for age, sex, field center, Hispanic or Latino background, systolic blood pressure, low-density lipoprotein cholesterol, body mass index, smoking status, alcohol use, educational level, employment status, income, sleep duration, diet, language preference, accelerometer wear time, recent physician visit, and use of health insurance.All models were adjusted for complex survey design.Interaction terms were not statistically significant although effect sizes appeared different between the 2 glycemic categories.
despite their success in slowing progression to diabetes, the interventions were not successful in reducing all-cause or cardiovascular mortality, except possibly stroke. 36The intervention and follow-up periods may have been too brief to influence mortality. 36When follow-up of the Da Qing study was extended to 23 years 44 and to 30 years, 45 with mean (SD) ages reaching 71.8 (6.9) years (control group) and 70.5 (6.6) years (intervention group), the trial found reduced CVD risk and CVD-related mortality in their lifestyle intervention group compared with the control group (routine advice).
What may explain our observation that decreased PA was associated with mortality and CVD risk in normoglycemia but not significantly so in prediabetes?First, common comorbidities with prediabetes may be relatively resistant to lifestyle changes.In HCHS/SOL, we previously observed favorable 6-year patterns in LDL-C level with lower sedentary behavior, but only in the absence of diabetes, prediabetes, and CVD. 46Greater use of medications (antihypertensives, lipid-lowering agents) in prediabetes than in normoglycemia may overshadow the influence of lifestyle on CVD or mortality risk.
Second, chronic inflammation and undiagnosed conditions may be more common in individuals with prediabetes than with normoglycemia, 4 possibly limiting their activity or increasing risk of adverse events from intense exercise.The threshold of exercise intensity needed to improve cardiorespiratory fitness may vary depending on fitness level, so intensity is difficult to define from accelerometry. 47Thus, total PA volume may be more important than intensity in persons with prediabetes.This could partially explain our finding of higher (albeit nonsignificant) HRs for the association of increased sedentary behavior with CVD and mortality risk in both glycemic groups, since sedentary behavior reflects the complement of total time in any measured PA intensity.
Third, activity level could be differentially misclassified between prediabetes and normoglycemia groups.Activity was measured at baseline, and participants may have changed Estimated hazard ratio (95% confidence interval) for the association of the combined outcome of all-cause mortality or incident CVD event with binary PA/sedentary behavior exposure by glycemic status, FHS and HCHS/SOL, minimally adjusted models eTable 5. Baseline characteristics at low and high sedentary behavior levels, HCHS/SOL eTable 6. Baseline characteristics at low and high counts per minute, HCHS/SOL eTable 7. Baseline characteristics at steps Ն7000/d vs <7000/d, HCHS/SOL eTable 8. (A) Estimated hazard ratios (95% confidence intervals) for the association of the combined outcome (allcause mortality or incident CVD event) with continuous PA or sedentary behavior exposures by glycemic status, HCHS/SOL; (B) Analogous HR for sedentary behavior, steps and CAEE for combined glycemic groups eTable 9.Estimated hazard ratios (95% confidence intervals), with additional exclusions as a sensitivity analysis, for the association of the composite outcome of all-cause mortality or first incident CVD event with PA levels (PAG not met as exposure vs met as reference) by glycemic status in HCHS/SOL eTable 10.Estimated hazard ratios (95% confidence intervals), with additional exclusions as a sensitivity analysis, for the association of the composite outcome of all-cause mortality or first incident CVD event with PA levels (PAG not met as exposure vs met as reference) by glycemic status in FHS SUPPLEMENT 2.

Figure 1
Figure 1 depicts sample derivation for both cohorts.We excluded participants who had prevalent diabetes or CVD at baseline or the index examination, in 2008 through 2011 for HCHS/SOL, and in 2008 through 2011 (examination 2, Gen 3, NOS and Omni 2) or in 2011 through 2014 (examination 9

Figure 1 .
Figure 1.Sample Derivation for Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and Framingham Heart Study (FHS)

Table 1 .
Baseline Characteristics in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and Framingham Heart Study (FHS) Pooled Sample, by Glycemic Status (Table1).In HCHS/SOL, individuals with prediabetes vs normoglycemia had shorter sleep duration and higher Alternative Healthy Eating Index 2010 scores (range, 0 [nonadherence] to 110 [perfect adherence]), while these variables were similar between prediabetes and normoglycemia in FHS.In both glycemic groups, BMI was higher in HCHS/SOL than in FHS.Compared with FHS participants, HCHS/SOL participants were younger and more likely to meet PAG.In both cohorts, meeting PAG Physical Activity, CVD, and Mortality by Glycemic Status in Hispanic and Non-Hispanic Adults was associated with favorable socioeconomic and behavioral variables (eTables 1 and 2 in Supplement 1).

Table 1 .
Baseline Characteristics in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and Framingham Heart Study (FHS) Pooled Sample, by Glycemic Status (continued) a Continuous variables are reported as survey-adjusted mean (SE) or median (IQR).Categorical variables are reported as weighted percentages (95% CI).b Pooled sample from FHS comprises generation (Gen) 2, Gen 3, Omni 1, Omni 2, and NOS; continuous variables are reported as mean (SD) or median (Q1, Q3).Categorical variables are reported as No. (%).c Values of P from survey adjusted T tests for continuous variables and χ 2 tests for categorical variables.d Employment status, SF-12 General Health score (range 1-5, with higher scores indicating self-report of poorer health), SF-12 Pain score (range 1-5, with higher scores indicating more interference of pain with normal work), CESD-10 score (range 0-30, Figure 2. Hazard Ratios for the Composite Outcome of All-Cause Mortality and Incident Cardiovascular Disease With Sufficient (Reference) vs Insufficient (Exposure) Moderate to Vigorous Physical Activity to Meet 2018 Physical Activity Guidelines, by Glycemic Status in the Framingham Heart Study (FHS) and Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

Table 2 .
Association of Composite Outcome of All-Cause Mortality or First Incident Cardiovascular Disease Event With Binary Levels of PA or Sedentary Behavior by Glycemic Status in the Hispanic Community Health Study/Study of Latinos a Figure 3. Association of the Composite Outcome of All-Cause Mortality or First Incident Cardiovascular Disease Event With Each Tertile of Physical Activity (PA) or Sedentary Behavior Exposure by Glycemic Status in the Hispanic Community Health Study/Study ofLatinos Gong Q, Zhang P, Wang J, et al; Da Qing Diabetes Prevention Study Group.Morbidity and mortality after lifestyle intervention for people with impaired glucose tolerance: 30-year results of the Da Qing Diabetes Prevention Outcome Study.Lancet Diabetes Endocrinol.2019;7(6):452-461.doi:10.1016/S2213-8587(19)30093-246.Mossavar-Rahmani Y, Hua S, Qi Q, et al.Are sedentary behavior and physical activity independently associated with cardiometabolic benefits?the Hispanic Community Health Study/Study of Latinos.BMC Public Health.2020; 20(1):1400.doi:10.1186/s12889-020-09497-547.Garber CE, Blissmer B, Deschenes MR, et al; American College of Sports Medicine.American College of Sports Medicine position stand: quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise.Med Sci Sports Exerc.2011;43(7):1334-1359. doi:10.1249/MSS.0b013e318213fefb48.Mossavar-Rahmani Y, Lin J, Pan S, et al.Characterizing longitudinal change in accelerometry-based moderateto-vigorous physical activity in the Hispanic Community Health Study/Study of Latinos and the Framingham Heart Study.BMC Public Health.2023;23(1):1614.doi:10.1186/s12889-023-16442-949.U.S. Department of Health and Human Services.2018 Physical Activity Guidelines Advisory Committee scientific report.Accessed March 14, 2024.https://health.gov/sites/default/files/2019-09/PAG_Advisory_Committee_Report.pdf50.Troiano RP, Berrigan D, Dodd KW, Mâsse LC, Tilert T, McDowell M. Physical activity in the United States measured by accelerometer.Med Sci Sports Exerc.2008;40(1):181-188.doi:10.1249/mss.0b013e31815a51b351.Cao Z, Li W, Wen CP, et al.Risk of death associated with reversion from prediabetes to normoglycemia and the role of modifiable risk factors.JAMA Netw Open.2023;6(3):e234989.doi:10.1001/jamanetworkopen.2023.4989Details of methods for calibrated activity-related energy expenditure models eTable 1. Baseline characteristics by 2018 PAG Met/Not Met, HCHS/SOL eTable 2. Baseline characteristics by 2018 PAG Met/Not Met, FHS eTable 3. Number of incident events stratified by prediabetes status, FHS and HCHS/SOL eTable 4.
1Data from 9456 participants were analyzed except for steps (n = 9421).All models were adjusted for complex survey design.Reference levels were set to be the highest PA or lowest sedentary behavior level.Cutoffs for moderate to vigorous PA (MVPA) were mean minutes per day of 9.33 or lower for low, more than 9.33 to 26.00 for middle, and more than 26.00 for high.Cutoffs for mean counts per minute (CPM) were 116 or lower for low, 116 to 189 for middle, and higher than 189 for high.Cutoffs for mean steps per day were 5090 or fewer for low, 5090 to 8460 for middle, and more than 8460 for high.Cutoffs for sedentary behavior were mean minutes per day of 607 or less, more than 607 to 780 for middle, and more than 780 for high.HR indicates hazard ratio.45.